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G D Braunstein

Publications and source records attributed to G D Braunstein.

At least 37 records · Page 2Linked to original sources
PubMed1995

Production of superoxide dismutase, beta 2-microglobulin and ubiquitin by human term decidua in vitro.

In order to study decidual proteins produced during pregnancy, decidual cells were isolated from term placental membranes by collagenase digestion and Percoll gradient centrifugation. Serum-free CMRL-1066 medium, conditioned for 148 h with the purified decidual cells, was collected and concentrated by ultrafiltration and applied to a Sephadex G-50 column. The protein-containing fractions from the column were concentrated, dialyzed, lyophilized, applied to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and transferred to a polyvinylidene difluoride membrane, followed by sequencing. Superoxide dismutase and two new members of the decidual protein family, beta 2-microglobulin precursor and ubiquitin, were identified by 100% N-terminal sequence homology, and similarities of molecular weights and residue contents.

Amino Acid Sequence↗
PubMed1994

Thyroid incidentalomas. Prevalence by palpation and ultrasonography.

BACKGROUND: Thyroid nodules are commonly identified on autopsy examination. There are relatively few descriptions, however, of the frequency with which thyroid nodules are encountered incidentally during the course of other investigations. METHOD: Prospective study to examine the prevalence of thyroid nodules in asymptomatic North American subjects, with palpation findings compared with findings on high-resolution ultrasonography. RESULTS: Palpable nodules were identified in 21 (21%) of 100 subjects, with nine solitary nodules (9%) and 12 multiple nodules (12%). In comparison, only 33 subjects were found to be free of any nodules by ultrasonography. Of the 67 subjects with abnormal ultrasound findings, 22 had solitary nodules (22%) and 45 had multiple nodules (45%). The prevalence of nodules was greater in women (72%) than in men (41%) (P < .02). A concordance rate of 49% was noted between ultrasound and findings by palpation. CONCLUSIONS: The data indicate that thyroid abnormalities are very common incidental findings, emphasizing the need for a conservative approach when such lesions are encountered incidentally.

Adult↗
PubMed1994

The beta-core fragment of chorionic gonadotropin is not complexed to macromolecules in amniotic fluid.

A prior report claimed that amniotic fluid contains substantial quantities of beta-core fragment, a major degradation product of CG metabolism, complexed to macromolecules. In an attempt to confirm this finding, we measured beta-core fragment concentrations in 36 second- and 22 third-trimester amniotic fluid samples in a direct beta-core fragment RIA as well as a total CG RIA and found that all of the apparent immunoreactivity could be accounted for by the cross-reaction of CG and CG beta in the beta-core fragment RIA. Chromatography of concentrated pools of amniotic fluid or pregnancy serum failed to reveal a peak of CG immunoreactivity in the beta-core fragment elution area. However, chromatography after incubation of amniotic fluid or pregnancy serum with 3 mol/L ammonium thiocyanate resulted in a peak of apparent CG immunoreactivity in the area coinciding with the elution of ammonium thiocyanate and not purified beta-core fragment. The addition of ammonium thiocyanate to the CG RIA tubes resulted in apparent, but spurious, CG immunoreactivity. We conclude that amniotic fluid does not contain appreciable amounts of free or complexed beta-core fragment. We also were unable to confirm the presence of beta-core fragment complexed to macromolecules in pregnancy serum. Our results suggest that the previous studies that purported to demonstrate beta-core fragment-macromolecular complexes in amniotic fluid and pregnancy serum were reporting artifacts introduced by the ammonium thiocyanate used to dissociate beta-core fragment from the putative complex or the in vitro generation of beta-core fragment.

Amniocentesis↗
PubMed1994

Gonadotropin-releasing hormone-dependent chorionic gonadotropin secretion in a menopausal woman.

We report the evaluation of a 46-yr-old asymptomatic menopausal woman whose serum hCG concentrations remained persistently supra-normal for 3 yr (mean +/- SD, 20 +/- 10 IU/L; n = 19). Holo-hCG and beta-core fragments were detected in the patient's urine by Ultragel chromatography, followed by specific RIAs. Trophoblastic, germ cell, and other malignancies appeared to be excluded by the absence of serum tumor markers and imaging procedures of the pelvis, abdomen, breast, and chest. Administration of a single bolus dose of synthetic GnRH (100 micrograms) increased the serum hCG concentration by 50% (from 26 to 40 IU/L). Administration of the Nal-Glu GnRH antagonist (5 mg, sc, every 12 h for 1 week) decreased the serum hCG concentration from 27 to 4.6 IU/L. The pronounced decrease in the serum hCG concentration during antagonism of the action of endogenous GnRH by administration of Nal-Glu GnRH suggests that the pituitary is the source of the supra-normal serum hCG concentrations, because the pituitary is exposed to the highest concentration of endogenous GnRH.

Adult↗
PubMed1994

Four rapid serum-urine combination assays of choriogonadotropin (hCG) compared and assessed for their utility in quantitative determinations of hCG.

We evaluated the performance of four visually read pregnancy tests (TestPack Plus hCG Combo, ICON II hCG, SureCell hCG-Serum/Urine and PregnaGen 1-Step) designed to detect increased concentrations of choriogonadotropin (hCG) in either serum or urine samples. The biochemical sensitivities and specificity in both serum and urine samples were similar for each kit. All kits correctly identified pregnancy serum samples: The TestPack Plus hCG Combo and SureCell hCG-Serum/Urine were 100% specific; the other two kits exhibited a few false-positive results. For urine samples the ICON II hCG test was 100% sensitive, and the other three were 99.5% sensitive, with false-positive urine results occasionally reported by the PregnaGen 1-Step and ICON II hCG tests. Quantitative hCG concentrations could be estimated in pregnancy serum samples, but not urine samples, through determination of the time elapsed from the sample application or addition of the final reagent to the first appearance of a positive result.

Chorionic Gonadotropin↗
PubMed1993

Gynecomastia.

Explore the source record for details and available documents.

Androgens↗
PubMed1993

Selecting human chorionic gonadotropin immunoassays: consideration of cross-reacting molecules in first-trimester pregnancy serum and urine.

OBJECTIVE: We investigated the variation in human chorionic gonadotropin results found with different commercial kits. Levels of human chorionic gonadotropin and related molecules were determined in pregnancy serum and urine and compared with the specificities of different laboratory, office, and home test kits. STUDY DESIGN: Total human chorionic gonadotropin (nicked+nonnicked), nonnicked human chorionic gonadotropin, free beta subunit, and beta core fragment were measured in 242 serum samples and 125 urine samples from early pregnancies. RESULTS: In serum, in the 2 weeks after the missed period when most pregnancy tests are performed, median levels of total, nonnicked, and beta human chorionic gonadotropin (total+free beta+beta core) were similar (< or = 12% difference). Individual values, however, varied significantly. For nonnicked human chorionic gonadotropin, values ranged from 41% to 145% and for beta from 101% to 145% of the total human chorionic gonadotropin level. In urine individual nonnicked values varied from < 1% to 148% and beta values from 102% to 547% of the total human chorionic gonadotropin level. A survey of 29 kits revealed that 10 were types detecting total human chorionic gonadotropin, five detecting nonnicked only, and 14 were beta assays. CONCLUSIONS: Results from total, nonnicked, and beta human chorionic gonadotropin kits are not necessarily interconvertible. Individual variations in levels of nicked human chorionic gonadotropin, free beta and beta core, and differences in their recognition by immunoassays causes discordant results.

Chorionic Gonadotropin↗
PubMed1993

The deactivation of hCG by nicking and dissociation.

Human chorionic gonadotropin (hCG) is composed of an alpha- and a beta-subunit, joined noncovalently. A proportion of hCG molecules in pregnancy serum and urine samples have nicks or a missing peptide linkage between either beta-subunit residues 44 and 45 or beta-subunit residues 47 and 48. These nicks ablate the steroidogenic activity of hCG. We examined the source of nicking, and the occurrence and stability of nicked hCG molecules produced during pregnancy. We investigated the source of nicking. Standard hCG was added to three samples of whole blood, and incubated 18 h at 37 C. No change in extent of nicking was detected. However, nicking of hCG beta-subunit was detected by gel electrophoresis (bands at M(r) = 17,000 and M(r) = 22,000, corresponding to the peptides beta 1-47(44) and beta 48(45)-145, respectively) in culture fluids from first trimester placental explants and from JAr malignant trophoblast cells. We inferred that nicking occurs before or immediately upon secretion by trophoblast tissue. We examined the occurrence of nicking. Levels of total hCG (nicked+nonnicked) and intact hCG (nonnicked) were determined in 233 serum and 168 urine samples from 4-40 weeks of pregnancy. From the two measurements the extent of nicking was estimated. A linear relationship was indicated between advancing weeks of gestation and increasing extent of nicking (regression analysis, months vs. percent nicked, 95% correlation). Minimum nicking was observed in serum from the first 2 months of pregnancy (mean = 9% of hCG molecules), increased nicking in the months after, and maximum nicking in samples from the last 2 months of pregnancy (mean = 21% of hCG molecules, t test first 2 months vs. last 2 months, P < 0.00005). Similar results were observed with urine samples (first 2 months mean = 9%, last 2 months = 27%, t test P < 0.00005). We concluded that nicking is more prevalent after the hCG peak (after 2 months of pregnancy). Finally, we examined the stabilities of nicked and intact hCG molecules. Standard hCG (batch CR127, 20% nicked) and hCG preparation C5 (100% nicked) were incubated for varying times in whole blood. C5 hCG dissociated rapidly into free alpha- and beta-subunits (dissociation half-life 22 +/- 5.2 h), over 30 times faster than standard hCG (dissociation half-life 700 h).(ABSTRACT TRUNCATED AT 400 WORDS)

Choriocarcinoma↗
PubMed1993

Radiation-associated hyperparathyroidism: comparison of adenoma growth rates, inferred from weight and duration of latency, with prevalence of mitosis.

In sporadic parathyroid adenomas, the birth rate of new cells, based on the proportion of S-phase cells at the time of surgical excision, is much too low to account for growth of the tumor from a single cell, as is required by monoclonal origin, even if the mutation occurred in utero, indicating that the rate of cell proliferation has slowed down during the course of the disease. In radiation-associated hyperparathyroidism, the age at irradiation provides a more accurate upper limit to the age of the tumor. The purpose of this study was to relate this age to the prevalence of mitosis as an alternative index of current cell proliferation. In 56 such patients, the geometric mean for the minimum cell birth rate needed for growth from a single cell to the observed size in the time available was 54.4%. In 44 patients, including 31 of the previous 56 and an additional 13, sampling an average of 220,000 cell profiles, 15 mitoses were found, an overall prevalence of 0.15/10(5), which corresponds to a cell birth rate of 2.7%/yr, assuming the duration of mitosis to be 0.5 h. If cases with no mitosis were assigned a value of half the detection limit, the geometric mean mitotic index was 0.360/10(5), and the corresponding cell birth rate was 6.4%/yr. This is more than 8 times smaller than the minimum birth rate required and 20 times smaller than the cell birth rate in meningiomas, suggesting that such extreme reduction of cell birth rate is a unique feature of parathyroid adenomas, rather than a general feature of all benign tumors. The data support the set-point hypothesis, which reconciles the earlier concept of focal hyperplasia with monoclonal origin and provides an alternative nonneoplastic mechanism of etiology for the usual nonprogressive form of the disease.

Adenoma↗
PubMed1992

Do thyroid function tests independently predict survival in the critically ill?

We studied the ability of thyroid function tests to predict hospital survival in 116 critically ill patients and compared the results with independent predictions of survival made by critical care physicians. Eleven patients (9.5%) had clinically unsuspected hypothyroidism and were less likely to survive (p = 0.03). In patients critically ill with nonthyroidal disease, low T3, low FT3I, low T4, low FT4I, high TSH, and high T3U levels each showed significant correlation with nonsurvival (all p less than 0.02). Of these, however, only low T3 (p less than 0.001) and high TSH (p = 0.016) showed significant independent prediction of nonsurvival, and only low T3 (p = 0.011) added any significant independent prediction of nonsurvival beyond that made clinically by the group of critical care physicians.

Critical Illness↗
PubMed1992

Somatostatin analog induces insulin-like growth factor binding protein-1 (IGFBP-1) expression in human hepatoma cells.

As the somatostatin analog octreotide suppresses pituitary GH secretion and circulating IGF-1 levels, we examined its effects on human hepatoma (hep G2) cells which selectively express IGFBP-1. Octreotide (60 nM) stimulated IGFBP-1 up to 4.1-fold (p < 0.001 after 24 hrs). Induction of IGFBP-1 was first detectable after 12 hrs of 6 nM octreotide (1.5-fold, p < 0.03), and was confirmed by ligand blotting. Cholera toxin and forskolin induced IGFBP-1 independently and were also additive with octreotide. IGFBP-1 mRNA expression was induced 2.7-fold by octreotide. Thus, octreotide induces basal and stimulated IGFBP-1 in hepatocytes independently of insulin and GH. As IGFBP-1 may regulate peripheral IGF-1 action, induction of IGFBP-1 represents a novel pituitary-independent mechanism for octreotide action.

Blotting, Northern↗
PubMed1992

Octreotide stimulates insulin-like growth factor-binding protein-1: a potential pituitary-independent mechanism for drug action.

As the long-acting somatostatin analog octreotide attenuates polypeptide hormone hypersecretion, it has recently been used to effectively treat acromegaly and gastrointestinal carcinoid tumors. Most growth-promoting actions of GH are mediated by insulin-like growth factor-I (IGF-I), which circulates complexed with multiple binding proteins (IGFBPs). IGFBP-1, a nonglycosylated peptide, competes with the IGF-I receptor for ligand binding and also regulates IGF action. To examine GH-independent mechanisms for octreotide regulation of the GH axis, circulating levels of IGFBP-1 were measured hourly after sc octreotide or saline administration in normal and GH-deficient adults. As IGFBP-1 is inhibited by insulin and GH, the dynamic pattern of alterations in GH and insulin levels was also assessed. After octreotide (100 micrograms) administration to 10 normal subjects, mean IGFBP-1 concentrations were stimulated from 23 +/- 4 to 72 +/- 18 micrograms/L (P < 0.007 vs. saline) after 2 h. Maximal induction of IGFBP-1 levels occurred after 3 h (325 +/- 115 micrograms/L; P < 0.02 vs. saline) and remained elevated (P < 0.005) for 6 h. IGFBP-1 was induced by octreotide in all subjects and was confirmed by Western ligand blotting. Insulin and GH levels preceding the rise in IGFBP-1 were unaltered by octreotide. Octreotide stimulated IGFBP-1 5-fold during a sustained fast in 4 normal subjects, despite equally suppressed insulin levels in both saline- and octreotide-treated groups. In 4 GH-deficient adults, IGFBP-1 levels were stimulated by octreotide from 16 +/- 3 to 146 +/- 36 and 154 +/- 28 micrograms/L after 3 and 4 h, respectively. In conclusion, the somatostatin analog octreotide induces IGFBP-1 independently of GH and insulin. As IGFBP-1 regulates the action of IGF-I, octreotide stimulation of IGFBPs may represent an additional pharmacological mechanism for attenuating the GH-IGF-I axis.

Adolescent↗
PubMed1991

Effects of anabolic-androgenic steroids on muscular strength.

OBJECTIVE: To assess the effects of anabolic-androgenic steroids on human muscle strength. DATA SOURCES: A MEDLINE search for the period from January 1966 to April 1990, supplemented by manual searches of previous reviews, produced 30 studies in which subjects received more than one dose of the study steroid and in which changes in muscular strength were measured. STUDY SELECTION: Of the 30 studies, 14 were not included in the detailed data summary because they did not use a placebo control, did not randomize subjects to groups, or did not make objective strength measurements, or because percent change in strength data could not be abstracted. DATA EXTRACTION: Details of study design, reporting of results, and the adequacy and correctness of statistical methods were tabulated. Percent improvement in strength for the largest muscle group studied was computed, using the difference between results for the placebo and for the steroid-treated groups. DATA SYNTHESIS: Previously trained athletes show slightly greater improvements in strength in the anabolic-androgenic steroid-treated group than in the placebo group, with a median difference of 5% across the nine studies (range, 1.2% to 18.7%). A meta-analysis of the three studies with enough information to compute effect size showed a mean difference of 1.0 standard deviations (95% CI, 0.49 to 1.5). However, the poor overall quality of the studies in terms of design, sample size, and analysis; the lack of a dose-response effect across the narrow range of dosages tested; and the tendency for differences to be smaller in the larger studies throw these results into question. No evidence was found to support enhanced muscle strength with steroid use in eight studies in untrained normal volunteers. CONCLUSIONS: Anabolic steroids may slightly enhance muscle strength in previously trained athletes. No firm conclusion is possible concerning the efficacy of anabolic steroids in enhancing overall athletic performance. Results for the low steroid dosages studied in the published reports cannot be generalized to steroid-using athletes taking megadose regimens.

Anabolic Agents↗
PubMed1991

Pediatric germ cell and human chorionic gonadotropin-producing tumors. Clinical and laboratory features.

Germ cell tumors may cause various aberrations in pubertal development. In prepubertal boys, these tumors may secrete human chorionic gonadotropin, resulting in precocious puberty. Human chorionic gonadotropin and alpha-fetoprotein are both useful as germ cell tumor markers in the diagnosis and detection of recurrence. Pregnancy-specific beta 1-glycoprotein, another oncoplacental antigen, has been used as a tumor marker for trophoblastic neoplasms, but not previously for human chorionic gonadotropin-producing tumors associated with precocious puberty. Patients with germ cell tumors may also have abnormal karyotypes. Herein, we describe six male pediatric patients with germ cell tumors and pubertal derangements seen during an 8-year period. We confirm the high incidence of associated sexual precocity, the usefulness of alpha-fetoprotein, human chorionic gonadotropin, and pregnancy-specific beta 1-glycoprotein as tumor markers in the diagnosis and follow-up of these patients, and the occurrence of sex chromosomal abnormalities.

Adolescent↗
PubMed1991

Decidua produces a protein that inhibits choriogonadotrophin release from human trophoblasts.

To test the hypothesis that uterine decidua may modulate trophoblast function, trophoblasts and decidual cells were isolated from term placentas by enzymatic digestion and Percoll gradient centrifugation. Placental trophoblasts were cocultured with decidual cells and trophoblasts or JEG-3 choriocarcinoma cells were incubated with medium conditioned by decidual cells (DCM) for 72-96 h. In cocultures decidual cells inhibited choriogonadotropin (hCG) release from trophoblasts by 75% in comparison with controls (P less than 0.001). The DCM contained a factor that markedly inhibited hCG release from trophoblasts and JEG cells in vitro compared with controls. The inhibitory effect of the factor on hCG release was dose dependent, and could be eliminated by boiling the DCM for 30 min or proteolytic enzyme treatment. Ultrafiltration and Sephadex G-50 fractionation of the DCM indicated that the apparent molecular mass was 7,000-10,000 D. DCM also inhibited the stimulatory effect of exogenous cAMP on hCG secretion by JEG-3 cells, suggesting that DCM may interfere with activation of the cAMP-dependent protein kinases or transcription of hCG genes. These results suggest that the release of trophoblast hCG is under local paracrine control, regulated in part by a protein released by decidual cells.

Cells, Cultured↗